September 7, 2016
Cody Knight was15 years old when he came down with a serious intestinal infection caused by the bacterium Clostridium difficile (C. diff). Despite antibiotic treatments, the infection kept coming back at least three times over a six-month period.
“My son lost 15 pounds and it took weeks for him to gain enough strength to do anything,” said his mother Holly Knight. “He missed the last week of school and never really got a chance to play freshman football due to his frequent bouts with vomiting and diarrhea. As a last resort, Cody received a fecal transplant two years ago at Texas Children’s which has improved his symptoms tremendously.”
To improve outcomes for C. diff patients like Cody, Texas Children’s Microbiome Research Center received a 5-year, $7.5 million grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH) to accelerate a multi-center study to combat C. diff, the most common and potentially deadly bacterial infection impacting children and adults in the U.S.
C. diff, a bacterium that causes diarrhea and severe inflammation of the colon, is a hospital-acquired infection often associated with inappropriate antibiotic use. While antibiotics are used to treat infections in children and adults, they can also disrupt the natural communities of healthy bacteria in the gut, allowing C. diff to colonize and cause disease.
“C. diff is a disorder of microbial ecology,” said Dr. James Versalovic, pathologist-in-chief and director of Texas Children’s Microbiome Center. “Some patients are more susceptible to C. diff recurrence following treatment with antibiotics while other patients may struggle with infections due to drug-resistant bacteria including C. diff. These issues can pose enormous challenges to successfully treating these patients.”
At Texas Children’s Hospital and Texas Children’s Pavilion for Women, our physicians are continuously challenged by many infectious agents and drug-resistant pathogens. Being at the leading edge of “big” discovery science requires a highly collaborative approach to uncover the causes of C. diff infection and drug resistance in children and women.
“This 5-year grant will accelerate our existing work in C. diff as it relates to the human microbiome,” said Dr. Tor Savidge, associate director of Texas Children’s Microbiome Center and principal investigator of this study. “Our long-term goal is to achieve a better understanding of why certain patients fail antibiotic treatment and which patients are more susceptible to recurrences in order to help us develop new methods to treat C. diff infection.”
Using a systems biology approach and the latest state-of-the-art technologies, Savidge and his team – including research partners at Baylor College of Medicine, Texas A&M University, University of Houston, and UCLA – will analyze the stool specimens of C. diff patients at Texas Children’s and compare it to specimens of healthy adults and children. These researchers, who form an integral part of the C. diff Gulf Coast Collaborative, will also examine the common threads and differences between adults and children with C. diff infection. A unique aspect of this study is the inclusion of infants who are not susceptible to this pathogen.
“Babies in their first year of life may be colonized during infancy by C. diff,” Versalovic said. “Their microbiome develops very early in life but infants may or may not respond to the toxins produced by C. diff. We have much to learn about the susceptibility of young children to C. diff disease. We know that the numbers of children infected with C. diff have expanded greatly in the past 15 years.”
This collaborative study is a direct result of the Precision Medicine Initiative led by President Barack Obama designed to equip clinicians with the necessary resources to determine which treatments will work best for which patients based on specific characteristics like human genetic makeup, or in this case, the bacterial composition of a patient’s microbiome.
Texas Children’s is uniquely positioned as the leading research site for this study. Besides the Department of Pathology’s diagnostic capabilities to test for C.diff in children and women, Texas Children’s Microbiome Center has partnered with Dr. Richard Kellermayer from the Pediatric Gastroenterology, Hepatology and Nutrition section to offer fecal transplants as a treatment alternative for children with recurrent C. diff infection.
“It’s important for the medical community to be smarter about antibiotic use and its effects on the microbiome,” Savidge said. “I think some fundamental lessons will emerge in this 5-year study that will help us understand childhood infections and lifetime risk of serious infections further down the road.”
For Cody’s mom, she is grateful that Texas Children’s is leading this study and is hopeful that a cure for C. diff will one day be found.
“I met so many children and adults suffering with recurring C.diff when Cody was ill,” Knight said. “I support any research that can be done to prevent another child from being as sick as Cody was for such a long period of time.”
Norberto Montes, Medical Technologist for Pathology Department, died December 28, 2016 at the age of 68.
